Genomic profiling of tumors suggests that each cancer is genetically unique and future success in treatment will require highly individualized selection of therapy. However, the process of matching effective drugs to cancer genotypes is an inherently inefficient process. Typically, each drug is tested on a population of 50-200 patients having the matching genomic characteristics. However, many characteristics are rare, occurring in only a small fraction of patients, and some may be unique, when considering all the possible genetic modifiers. These considerations can make studies of these patient cohorts inefficient or impractical. One potential alternative is in vitro drug sensitivity testing where multiple drugs can be tested against each cancer. Unfortunately, in vitro drug sensitivity assays for cancer have been unsuccessful despite decades of effort. Simultaneous testing of many drugs in vivo on each patient would overcome significant barriers to the rapid and efficient development of effective drugs for individualized therapy.
A further barrier to individualized treatments is the problem of predicting sensitivity to existing treatments, which (though toxic) are effective in only a fraction of patients. One precedent for this approach is in bacterial sensitivity testing. In the 1950's Kirby and Bauer developed a method to test bacterial sensitivity to antibiotics. This simple and elegant test allows for the selection of specific and effective antibiotic therapies for each patient and is in routine clinical use today. Analogously, this process could be applied to cancer. Utilizing multiplexed drug delivery at the site of the cancer in cancer patients would allow for the identification of effective therapies, while sparing patients the toxicity of systemic administration of ineffective therapies. Unfortunately, the in vitro analog to the Kirby-Bauer test in cancer has not predicted benefit to chemotherapy, possibly due to the variability in which particular cancer cell clone grows in the lab or due to complex interactions between tumor cells and their environment within the human host.
As is known, current testing techniques are conducted in vitro despite the known importance of the tumor environment. By way of example, it is known that certain types of cancer cells, e.g. breast cancer cells, do not develop and metastasize without support from the local microenvironment. As such, it can be appreciated that the systemic use of in vitro testing (i.e. in the absence of an intact local microenvironment) likely prevents researchers from obtaining a complete understanding of a cancer's growth potential. Furthermore, in vivo, local tumor responses often predict the benefit of systemic therapy. Hence, it is highly desirable to provide a device which allows for the multiplexed point source administration of chemotherapeutic compounds in vivo.
Therefore, it is a primary object and feature of the present invention to provide a microfluidic device which may be used in the multiplexed point source administration of compounds (e.g. therapeutic, chemotherapeutic and anticancer compounds) in vivo.
It is a further object and feature of the present invention to provide a microfluidic device which may be used in the multiplexed point source administration of compounds that allows for the identification of effective therapies, while sparing patients the toxicity of systemic administration of ineffective therapies.
It is a still further object and feature of the present invention to provide a microfluidic device which may be used in the multiplexed point source administration of compounds that improves patient outcomes through more effective therapeutic decision making and accelerates the process of targeted drug development.
It is a still farther object and feature of the present invention to provide a microfluidic device which may be used in the multiplexed point source administration of compounds that is simple to utilize and inexpensive to manufacture.
It is a still further object and feature of the present invention to provide a microfluidic device which may be used in conjunction with other microfluidic devices to provide a multiplexed point source to administer multiple compounds simultaneously in vivo.
It is a still further object and feature of the present invention to provide a microfluidic device which may be installed within a human body, without any part protruding through the skin, to deliver a drug or a compound to a specific location over a period of days to weeks.
In accordance with the present invention, a device for the administration of a compound in a body is provided. The device includes a capsule having an inner surface defining a reservoir for receiving the compound therein. A diffusion regulator communicates with the reservoir. The diffusion regulator controls the diffusion of the compound from the reservoir into the body.
The capsule has opposite first and second ends. A seal is engageable with the first end of the capsule. The seal is configured for preventing the compound from exiting the reservoir through the first end of the capsule. The diffusion regulator includes a needle having a first end communicating with the reservoir and a second end receivable in the body. A retention structure projects from capsule. The retention structure is configured to retain the capsule at a desired location within the body. The retention structure may include at least one barb projecting from the second end of the capsule. The at least one barb is engageable with the body.
A delivery instrument is provided for positioning the capsule within the body. The delivery instrument includes a barrel, e.g. an elongated tube, having an inner surface defining a passage for receiving the capsule therein. A dispersal element, e.g. push rod, acts to expel the capsule from the barrel and into the body. For example, the push rod may be slideably received in a first end of the elongated tube. The push rod is engageable with the capsule for urging the capsule from the passage of the elongated tube through the second end thereof. A second end of the elongated tube may be beveled to facilitate the insertion of the elongated tube into the body.
In accordance with a further aspect of the present invention, a device is provided for the administration of a compound in a body. The device includes a capsule having a reservoir therein for receiving the compound therein. A delivery instrument is configured for positioning the capsule within the body. The delivery instrument includes a barrel having an interior adapted to receive the capsule therein. A dispersal element interacts with the capsule to selectively expel the capsule from barrel and into the body. A diffusion regulator communicates with the reservoir. The diffusion regulator controls the diffusion of the compound from the reservoir into the body. A retention structure projects from capsule. The retention structure is configured to retain the capsule at a desired location within the body.
The capsule has opposite first and second ends. A seal is engageable with the first end of the capsule. The seal is configured to prevent the compound from exiting the reservoir through the first end of the capsule. The diffusion regulator includes a needle having a first end communicating with the reservoir and a second end receivable in the body. The retention structure includes at least one barb projecting from the capsule. The at least one barb is movable from a first retracted position to a second extended position in response to the capsule being expelled from the barrel. The barrel may be defined by an elongated tube having an inner surface defining a passage for receiving the capsule therein. The dispersal element may include a push rod slideably received in the first end of the elongated tube. The push rod is engageable with the capsule for selectively urging the capsule from the passage of the elongated tube through the second end thereof. The second end of the elongated tube may be beveled to facilitate the insertion of the elongated tube into the body.
In accordance with a still further aspect of the present invention, a device is provided for the administration of a compound in a body. The device includes a capsule having a reservoir therein for receiving the compound therein. A diffusion regulator communicates with the reservoir. The diffusion regulator controls the diffusion of the compound from the reservoir into the body. A retention structure projects from capsule. The retention structure is configured to retain the capsule at a desired location within the body.
The capsule has opposite first and second ends. A seal is engageable with the first end of the capsule. The seal is configured to prevent the compound from exiting the reservoir through the first end of the capsule. The diffusion regulator includes a needle having a first end communicating with the reservoir and a second end receivable in the body. An injection structure is provided for injecting the capsule into the body. The retention structure includes at least one barb projecting from the capsule. The at least one barb is movable from a first retracted position to a second extended position in response to the capsule being injected into the body. The injection structure includes an elongated tube having an inner surface defining a passage for receiving the capsule therein. The injection structure further includes a push rod slideably received in the first end of the elongated tube. The push rod is engageable with the capsule for selectively urging the capsule from the passage of the elongated tube into the body through the second end thereof. The second end of the elongated tube may be beveled to facilitate the insertion of the elongated tube into the body.